To elucidate the relationship between virologic risk factors and immunologic and clinical progression in patients receiving monotherapy in protocol ACTG 175, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. Specifically, to determine, in patients who have been taking zidovudine (AZT) alone for a long time, whether it is beneficial to add lamivudine (3TC) to AZT or to switch to d4T alone, and also to determine, in patients who have been taking didanosine (ddI) alone for a long time, whether it is beneficial to add AZT or AZT/3TC to ddI.

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

280

Study Completion Date:

May 1998

Detailed Description:

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Patients with prior AZT experience only are randomized to receive either d4T alone or AZT/3TC. Patients with prior ddI experience only are randomized to receive ddI/AZT or ddI/AZT/3TC. PER AMENDMENT 8/27/96: The study has been extended 6 months and treatment will be available until March 15, 1997 at the latest. Each patient will have regularly scheduled 12 week safety visits during the extension period.

AS PER AMENDMENT 1/22/97: The study has been extended for approximately 16 additional weeks beyond the current 6-month extension. Subjects will be unblinded to their assigned regimen beginning 2/21/97 and will continue therapy for up to 16 weeks in open-label fashion. AS PER AMENDMENT 5/9/97: The study has been extended for an additional 8 weeks; study drug will not be provided after 9/15/97.

Completed AZT or ddI monotherapy on ACTG 175 and remained on that regimen during any subsequent interval.

Not reached an ACTG 175 endpoint prior to May 1, 1995.

Consent of parent or guardian if less than 18 years old.

PER AMENDMENT 8/27/96:

Patients must be on study/on treatment at the time the protocol study treatment is extended.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Grade 2 or worse peripheral neuropathy.

Malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

Anti-HIV drugs other than study drugs.

Biologic response modifiers.

Systemic cytotoxic chemotherapy.

Any drug known to affect glucuronidation and/or clearance of AZT.

Concurrent Treatment:

Excluded:

Radiation therapy other than limited local therapy to skin.

Patients with the following prior condition are excluded:

History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

Prior 3TC.

Acute therapy for an infection (other than HIV) or other medical illness within 14 days prior to study entry.

Current ethanol abuse.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000831